Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody

TLDR

A small fraction of HIV‑1–infected individuals develop broad, potent antibodies that bind conserved epitopes on Env, including the host receptor‑binding site, yet viruses usually mask key entry components, making such antibody binding unexpected. The study aims to define the epitope of a neutralizing antibody targeting the fusion peptide and to inform vaccine design. The authors determined crystal structures of the antibody in complex with the fusion peptide and Env to map the epitope and elucidate the binding mechanism. They report a neutralizing antibody isolated from an HIV‑1–infected individual that binds the fusion peptide of Env. Kong et al., Science, this issue p.

Abstract

An antibody to block viral fusion A small fraction of HIV-1–infected individuals develop broad and potent antibodies that bind the HIV-1 envelope protein (Env). These antibodies recognize a limited set of conserved epitopes on Env, such as Env's host receptor-binding site. Kong et al. now report a neutralizing antibody isolated from an HIV-1–infected individual that binds to the fusion peptide of Env. This is unexpected because viruses often try to mask such key components of their cell entry machinery from antibody attack. Crystal structures of the antibody bound to the fusion peptide and to Env itself define the epitope, provide insight into the specific mechanism of antibody binding, and may inform HIV-1 vaccine design. Science , this issue p. 828